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BACKGROUND:Peroxisome proliferator-activated receptor (PPARs) have been identified as ligand-activated transcription factors that belong to the nuclear receptor superfamily. It has been shown that an association exists between Proline 12 alanine (Pro12Ala) polymorphism of PPAR-GAMMA2 (PPAR-γ2) gene and increased risk of type 2 diabetes mellitus (T2DM) in different populations. Therefore, the present study was designed to investigate the association between Pro12Ala polymorphism of PPAR-γ2 gene and T2DM in an Iranian population.MATERIALS AND METHODS:Two hundred unrelated people, including 100 healthy controls and 100 diabetic patients were recruited diagnosed based on American Diabetes Association criteria. Blood samples were used for isolation of genomic deoxyribonucleic acid (DNA). Having extracted the genomic DNA from human blood leukocytes by means of High Pure polymerase chain reaction (PCR) Template preparation kit, we carried out polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on each blood sample. Then, Genomic DNA was digested by BstU-I restriction enzyme. Thereafter, restriction products were analyzed by means of Polyacrylamide gel electrophoresis and stained by Ethidium Bromide.RESULTS:We found that the frequency of Ala allele in healthy subjects was significantly higher than in diabetic subjects (P = 0003). Moreover, the genotype frequency of Ala/Ala in healthy subjects was significantly higher than in diabetic subjects (P < 0.001). However, the genotype frequency of Ala/Pro in diabetic subjects was significantly higher than in healthy subjects (P < 0.001).CONCLUSION:The present study suggests that polymorphism of PPAR-γ2 gene is associated with T2DM. Furthermore, Ala allele is significantly found in non-diabetic individual’s Iranian population.

Development of new medicine with fewer deleterious effects and more efficacies for treatment of inflammatory bowel disease is needed. 5-Hydroxytryptamine 3 receptor (5-HT 3 R) antagonists have exhibited analgesic and anti-inflammatory features in vitro and in vivo . The present study was designed to evaluate the anti-inflammatory effect of alosetron, a 5-HT 3 R antagonist, on trinitrobenzenesulfonic acid (TNBS)-induced ulcerative colitis in rats. Two h subsequent to induce colitis (intracolonic instillation of TNBS, 50 mg/kg) in male Wistar rats, alosetron (1 mg/kg), dexamethasone (1 mg/kg), meta-chlorophenylbiguanide (mCPBG, a 5-HT 3 R agonist, 5 mg/kg), or alosetron + mCPBG were administrated intraperitoneally for 6 days. Animals were thereafter sacrificed and the efficacy of drugs was evaluated macroscopically, histologically, and biochemically (myeloperoxidase, tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta) on distal colon samples. Treatment with alosetron and dexamethasone improved macroscopic and microscopic colonic damages significantly and decreased myeloperoxidase activity and colonic levels of inflammatory cytokines. The profitable effects of alosetron were antagonized by concurrent administration of mCPBG. Our data provided evidence that the protective effects of alosetron on TNBS-induced colitis can be mediated by 5- HT3R.

There is a pressing need for research that will lead to the reveal of targets designed to analyse the possible pathways for the treatment of IBD. Because of the probable involvement of serotonin in inflammatory conditions of intestine and the important role of 5HT4 receptors in GI function, the investigation of the role of 5HT4 receptors in the pathogenesis of IBD will be interesting. The aim of this study was to investigate the effects of cisapride, a 5HT4 receptor agonist, in trinitrobenzenesulfonic-acid-(TNBS) induced rat colitis. Two hours subsequent to induction of colitis using TNBS in rats, cisapride (2 mg/kg, intraperitoneally (i.p); 4 mg/kg, orally (p.o)) and dexamethasone (1 mg/kg, i.p; 2 mg/kg, p.o) were administrated for 6 days. Animals were thereafter euthanized; macroscopic, histological, and biochemical assessments and ELISA test were carried out on distal colon samples. Our data showed that dexamethasone treatment (i.p, p.o) significantly decreased macroscopic and microscopic damage and also biochemical markers, but there were no significant differences in aforementioned parameters between cisapride (i.p or p.o) and TNBS-treated rats. It can be deduced that because the severity of colitis produced by TNBS is massive (through various pathways), cisapride could not bring about more colitis damages through 5HT4 receptors. Based on the present study further researches are required for investigating the exact roles of 5HT4 receptors in the pathogenesis of ulcerative colitis.

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